Beyond Serum Creatinine: Detecting Early CKD in Cats Before Azotemia

A geriatric cat may appear clinically stable, yet renal function may already be changing. This creates a familiar clinical challenge: How early can chronic kidney disease (CKD) be detected before azotemia becomes obvious? 

CKD is common in older cats, with prevalence increasing from approximately 2%–4% in the overall feline population to 30%–40% in cats older than 10 years^[3],[4]. Yet traditional renal markers do not always identify kidney damage at an early stage. 

Why Serum Creatinine Can Miss Early Renal Dysfunction 

Serum creatinine (sCr) remains a practical renal biomarker because it is inexpensive, readily available, easy to measure, and has low intra-individual variability^[1],[2]. Serial sCr measurements can also help identify changes in renal function even when values remain within the reference range^[2],[3]. 

The limitation is sensitivity. 

Serum creatinine is strongly influenced by muscle mass, making interpretation more difficult when body condition varies^[4],[5],[6]. More importantly, sCr has relatively low sensitivity for detecting an early decrease in glomerular filtration rate (GFR). It also cannot identify kidney damage that has not yet reduced GFR^[7],[8]. 

This distinction matters clinically. Kidney injury can be developing before the conventional marker shows a clear abnormality. 

What About Urine Specific Gravity? 

Urine specific gravity (USG) provides another important piece of the renal assessment. Clinically, CKD is commonly recognized using a combination of compatible clinical signs, azotemia, and an inappropriate USG. A USG below 1.035 is considered abnormal in cats with dehydration or azotemia^[8]. 

However, USG is not an infallible indicator of CKD. 

Some cats with CKD can retain urinary concentrating ability. Conversely, dilute urine is not necessarily renal in origin. Diuretics, glucosuria, electrolyte disturbances, and liver disease can also produce inappropriate urinary dilution^[8]. 

Therefore, an apparently reassuring USG does not necessarily exclude early renal dysfunction, while dilute urine requires consideration of non-renal causes. 

Where Does SDMA Fit? 

The limitations of sCr have driven interest in alternative indirect markers of GFR, particularly symmetric dimethylarginine (SDMA). 

SDMA can increase with a smaller reduction in GFR than sCr, becoming elevated when GFR decreases by approximately 40% in cats^[8]. Unlike sCr, SDMA is not affected by muscle mass^{[9],[10],[11]}. This makes it particularly relevant when muscle mass can complicate interpretation of creatinine. 

But an increased SDMA value should not automatically be interpreted as definitive evidence of CKD. Breed-related differences have been identified, and available information regarding specificity remains limited^[8]. 

The International Renal Interest Society (IRIS) has incorporated SDMA into CKD staging, with persistent increases potentially indicating early CKD (IRIS stage 1). Persistence is important. Multiple blood samples may therefore be required when interpreting SDMA concentration^[8]. 

The Practical Approach: Look for the Pattern 

No single routine biomarker provides the complete picture of early renal disease. 

For a cat at risk of CKD, interpretation is stronger when sCr, SDMA, USG, and the clinical picture are considered together rather than relying on one result in isolation. 

A useful clinical approach is to ask: 

• Is sCr changing over time, even if it remains within the reference range? 
• Is SDMA persistently increased? 
• Is urinary concentration appropriate for the clinical context? 
• Could dilute urine have a non-renal explanation? 
• Do the findings collectively suggest an early change in renal function? 

Clinical Bottom Line 

Early feline CKD can be difficult to recognize because conventional markers primarily reflect changes in renal function rather than kidney injury itself. Serum creatinine remains useful, but its dependence on muscle mass and limited sensitivity for early GFR reduction are important limitations. SDMA may detect smaller reductions in GFR and can complement sCr, while USG adds information about urinary concentrating ability. 

For the individual cat, serial assessment and interpretation of multiple findings may provide a more informative picture than a single apparently normal renal marker.

References:

1. Paepe D, Daminet S. Feline CKD: diagnosis, staging and screening–what is recommended?. Journal of Feline Medicine and Surgery. 2013 Sep;15(1_suppl):15-27. https://journals.sagepub.com/doi/pdf/10.1177/1098612X13495235
2. Baral RM, Dhand NK, Freeman KP, Krockenberger MB, Govendir M. Biological variation and reference change values of feline plasma biochemistry analytes. Journal of Feline Medicine and Surgery. 2014 Apr;16(4):317-25. https://journals.sagepub.com/doi/pdf/10.1177/1098612X13508770
3. Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre HP, White J, Quimby J. ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease. Journal of feline medicine and surgery. 2016 Mar;18(3):219-39. https://journals.sagepub.com/doi/pdf/10.1177/1098612X16631234
4. Hall JA, Yerramilli M, Obare E, Yu S, Jewell DE. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in healthy geriatric cats fed reduced protein foods enriched with fish oil, L-carnitine, and medium-chain triglycerides. The Veterinary Journal. 2014 Dec 1;202(3):588-96. https://www.academia.edu/download/51750841/Comparison_of_serum_concentrations_of_sy20170211-27337-1yhrit0.pdf
5. Reynolds BS, Concordet D, Germain CA, Daste T, Boudet KG, Lefebvre HP. Breed dependency of reference intervals for plasma biochemical values in cats. Journal of Veterinary Internal Medicine. 2010 Jul;24(4):809-18. https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1939-1676.2010.0541.x
6. Reynolds BS, Brosse C, Jeunesse E, Concordet D, Lefebvre HP. Routine plasma biochemistry analytes in clinically healthy cats: within-day variations and effects of a standard meal. Journal of feline medicine and surgery. 2015 Jun;17(6):468-75. https://journals.sagepub.com/doi/pdf/10.1177/1098612X14546920
7. Cowgill LD, Polzin DJ, Elliott J, Nabity MB, Segev G, Grauer GF, Brown S, Langston C, van Dongen AM. Is progressive chronic kidney disease a slow acute kidney injury?. Veterinary Clinics: Small Animal Practice. 2016 Nov 1;46(6):995-1013. https://rvc-repository.worktribe.com/OutputFile/1395071
8. Kongtasai T, Paepe D, Meyer E, Mortier F, Marynissen S, Stammeleer L, Defauw P, Daminet S. Renal biomarkers in cats: A review of the current status in chronic kidney disease. Journal of veterinary internal medicine. 2022 Mar;36(2):379-96. https://academic.oup.com/jvim/article-pdf/36/2/379/66666729/jvim16377.pdf
9. Hall JA, Yerramilli MV, Obare E, Yerramilli M, Jewell DE. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in cats with chronic kidney disease. Journal of veterinary internal medicine. 2014 Nov;28(6):1676-83. https://onlinelibrary.wiley.com/doi/pdf/10.1111/jvim.12445
10. Paltrinieri S, Giraldi M, Prolo A, Scarpa P, Piseddu E, Beccati M, Graziani B, Bo S. Serum symmetric dimethylarginine and creatinine in Birman cats compared with cats of other breeds. Journal of feline medicine and surgery. 2018 Oct;20(10):905-12. https://journals.sagepub.com/doi/pdf/10.1177/1098612X17734066
11. Langhorn R, Kieler IN, Koch J, Christiansen LB, Jessen LR. Symmetric dimethylarginine in cats with hypertrophic cardiomyopathy and diabetes mellitus. Journal of veterinary internal medicine. 2018 Jan;32(1):57-63. https://academic.oup.com/jvim/article-pdf/32/1/57/66672488/jvim14902.pdf